Usual Adult Dose for:

Usual Pediatric Dose for:

Additional dosage information:

Usual Adult Dose for Tuberculosis - Active

Initial intensive phase dose: 600 mg orally two times a week with at least 72 hours between doses for 2 months

Rifapentine should be administered by direct observation of therapy in combination with daily companion drugs (such as ethambutol, pyrazinamide, and streptomycin) during the initial treatment phase. The determination of the companion drugs should be made by the treating physician and depends on susceptibility testing results as well as treatment phase.

Continuation phase dose: Following the 2 month intensive phase, 600 mg orally once a week for at least 4 months

The continuation treatment phase may consist of rifapentine with isoniazid or an appropriate antituberculosis agent for susceptible organisms by direct observation therapy. The treating physician should consult current guidelines for additional direction on other possible components of the continuation phase as well as for directions on extending this phase.

Usual Pediatric Dose for Tuberculosis - Active

15 years or older:
Initial intensive phase dose: 600 mg orally two times a week with at least 72 hours between doses for 2 months

Rifapentine should be administered by direct observation of therapy in combination with daily companion drugs (such as ethambutol, pyrazinamide, and streptomycin) during the initial treatment phase. The determination of the companion drugs should be made by the treating physician and depends on susceptibility testing results as well as treatment phase.

Continuation phase dose: Following the 2 month intensive phase, 600 mg orally once a week for at least 4 months

The continuation treatment phase may consist of rifapentine with isoniazid or an appropriate antituberculosis agent for susceptible organisms by direct observation therapy. The treating physician should consult current guidelines for additional direction on other possible components of the continuation phase as well as for directions on extending this phase.

Pharmacokinetics study (n=2)12 years to less than 15 years weighing less than 45 kg:
Initial intensive phase dose: 450 mg orally two times a week with at least 72 hours between doses for 2 months

Continuation phase dose: 450 mg orally once a week for at least 4 months following the initial phase

Pharmacokinetics study (n=10)12 years to less than 15 years weighing 45 kg or more:
Initial intensive phase dose: 600 mg orally two times a week with at least 72 hours between doses for 2 months

Continuation phase dose: 600 mg orally once a week for at least 4 months following the initial phase

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Although the single-dose pharmacokinetic profiles of rifapentine and its active metabolite, 25-desacetyl rifapentine, are not significantly altered in patients with hepatic impairment compared to healthy individuals, therapy with rifapentine should be administered cautiously in such patients, since the drug is primarily eliminated by the liver. Dosage adjustments may be necessary if undue adverse effects occur.

Dose Adjustments

Data not available

Precautions

The American Thoracic Society, US Centers for Disease Control and Prevention, and Infectious Diseases Society of America currently do not recommend rifapentine use during the initial intensive phase of tuberculosis treatment. Experts suggest patients with pulmonary tuberculosis who have negative sputum smears following the initial treatment phase may receive rifapentine in combination with isoniazid for the continuation phase.

Rifapentine should not be used alone during the initial or continuation phases of antituberculosis therapy. As with all antituberculosis regimens, compliance with all drugs in rifapentine-containing therapies is critical, particularly during the initial treatment phase to ensure early sputum conversion; poor compliance during this phase is associated with late sputum conversion and a high relapse rate. Rifapentine should be used with caution in patients with cavitary pulmonary lesions and/or failure to convert sputum after the first two months of treatment or in those with proof of bilateral pulmonary disease due to higher rates of relapse.

The normally recommended once-weekly continuation phase dosage (in combination with isoniazid) should not be used in HIV-infected patients with pulmonary tuberculosis. A higher rate of relapse and/or failure was reported with the presence of rifampin-resistant organisms. Risk factors for relapse include low CD4 counts, the presence of pulmonary and extrapulmonary disease at baseline, azole antifungal use, and younger age. Rifapentine has not been studied as part of the initial regimen in HIV-infected patients with pulmonary tuberculosis.

Antituberculous treatments, including the rifamycins, are associated with hepatotoxicity. Patients with abnormal liver function tests and/or liver disease should only be given rifapentine after careful consideration of risks and benefits. If a decision is made to use the drug, liver function tests, especially serum transaminases, should be obtained prior to therapy and then every 2 to 4 weeks during therapy. Rifapentine should be discontinued if signs of hepatic injury occur or liver disease worsens.

Hyperbilirubinemia may occur as a result of the possible competition for excretory pathways between rifapentine and bilirubin. A moderate rise in bilirubin is not necessarily an indication for interrupting treatment but should be evaluated with the patient's overall clinical condition.

All patients treated with rifapentine should have baseline measurements of hepatic enzymes, bilirubin, a complete blood count and platelet count. Patients should be seen at least monthly during rifapentine therapy and should be specifically questioned concerning symptoms associated with adverse events. All patients with abnormalities should have follow-up, including laboratory testing, if required. Routine laboratory monitoring for toxicity in people with normal baseline measurements is generally not required. Therapeutic concentrations of rifampin have been reported to inhibit standard microbiological assays for serum folate and Vitamin B12. Similar drug-laboratory interactions should be considered for rifapentine; thereby, alternative assay methods should be considered.

Clostridium difficile associated diarrhea (CDAD) has been reported with almost all antibiotics and may potentially be life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea following rifamycin therapy. Mild cases generally improve with discontinuation of the drug, while severe cases may require supportive therapy and treatment with an antimicrobial agent effective against C difficile. Hypertoxin producing strains of C difficile cause increased morbidity and mortality; these infections can be resistant to antimicrobial treatment and may necessitate colectomy.

Rifapentine therapy should not be used in patients with porphyria. Rifampin has enzyme-inducing properties, including induction of delta amino levulinic acid synthetase. Isolated reports have associated porphyria exacerbation with rifampin use. Based on these isolated reports coincident with rifampin use, it may be assumed that rifapentine has a similar effect.

Clinical studies of rifapentine did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for elderly patients should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Safety and efficacy have not been established in pediatric patients less than 12 years of age.

Dialysis

Data not available

Other Comments

Rifapentine should be taken with meals to increase oral bioavailability. Administration with a meal may also reduce gastrointestinal upset, nausea, and/or vomiting.

Pyridoxine is recommended with isoniazid to prevent the occurrence of peripheral neuropathy. Nutritional deficiency, HIV infection, renal failure, alcoholism, pregnancy, and breastfeeding are conditions that may predispose the patient to neuropathy.